Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential adverse consequences of increased adrenergic nervous system activity in patients with heart failure are now recognized. Modulation of the plasma noradrenaline response to submaximal exercise should be desirable. The long-term (9 weeks) effects of milrinone (10 mg 4 times a day) or captopril (50 mg 3 times a day) compared to placebo were evaluated in a double-blind crossover study, in 16 patients with stable, congestive heart failure receiving digoxin and furosemide. After treatment, clinical status (score range 0 to 14 points) improved significantly with both milrinone (4.4 +/- 0.5, p less than 0.01) and captopril (4.1 +/- 0.4, p less than 0.01). Plasma noradrenaline at rest was similar with both drugs and not significantly different from placebo. During submaximal exercise it increased significantly to 1,228 +/- 58 pg/ml with placebo and to 1,295 +/- 174 pg/ml with milrinone; this response was reduced significantly with captopril, to 820 +/- 100 pg/ml (p less than 0.01). Thus, long-term therapy with both captopril and milrinone improved the clinical score, but only captopril reduced the plasma noradrenaline response to submaximal exercise. These findings suggest that angiotensin-enzyme inhibition with captopril will modulate the adrenergic system response to daily activities in patients with chronic congestive heart failure and therefore could have additional salutary effects beyond vasodilatation.
 ...
PMID:Effects of captopril versus milrinone therapy in modulating the adrenergic nervous system response to exercise in congestive heart failure. 217 84

In 14 patients with heart failure (New York Heart Association class 2-3) and sinus rhythm the carotid sinus baroreceptors were stimulated to induce a reflex mediated decrease of sympathetic efferent activity and a simultaneous increase in vagal tone. Five patients were in severe heart failure (New York Heart Association class 3) with raised plasma concentrations of noradrenaline at rest (2.99 (0.86) nmol/l (mean (SD)) and nine patients had less severe heart failure (class 2.2 (0.2)) and normal plasma concentrations of noradrenaline at rest. The haemodynamic responses during arterial baroreceptor stimulation were different in both groups. In all five patients with severe heart failure cardiac output increased whereas in the nine patients with less severe heart failure it was unchanged or decreased. The increase of cardiac output in the group with severe heart failure was solely the result of a significant increase of stroke volume index (by 9 (2) ml/m2). In the nine patients with less severe heart failure stroke volume remained unchanged but heart rate decreased significantly by 7 (2) beats/min during baroreceptor stimulation. These data show that an integrated change of autonomic activity consisting of a decrease in sympathetic tone and an increase in vagal activity leads to an increase of stroke volume in patients with severe heart failure and hence to haemodynamic improvement.
 ...
PMID:Haemodynamic changes caused by alteration of autonomic activity in patients with heart failure. 218 68

The syndrome of heart failure results from inappropriate sodium and water retention by the kidneys which results, at least in part, from changes in renal haemodynamics. Renal blood flow at rest in heart failure is reduced in proportion to the reduction in cardiac output and falls dramatically during exercise as the cardiac output is redistributed to the exercising muscles. Both these phenomena are associated with a rise in plasma noradrenaline concentration. Afferent arteriolar tone is partly controlled by alpha-adrenoceptor stimulation while stimulation of beta 2-receptors will stimulate renal release of renin; through the elaboration of angiotensin II, profound effects on extra- and intra-renal vascular tone can occur. Although alpha-adrenoceptor stimulation can result in coronary vasoconstriction and a fall in coronary blood flow in patients with heart failure due to underlying atheromatous coronary heart disease, increased myocardial oxygen demand as the result of beta 1 (and cardiac beta 2) simulation may be more relevant. The control of limb blood flow is of great importance symptomatically. The systemic vasoconstriction that typifies the severe heart failure state has been a target for many vasodilatory interventions including alpha 1-receptor blockade and beta 2-receptor stimulation. Unfortunately, there is little evidence that such treatment leads to any specific increase in muscle blood flow either at rest or during exercise. In severe heart failure, sympathetic activity is increased at rest leading to vasoconstriction in several vascular beds, while in milder heart failure, excessive sympathetic stimulation is evident only during exercise. In either circumstance, however, it is evident that certain advantages may accrue from modulation of this excessive sympathetic activity.
 ...
PMID:Sympathetic activity and regional blood flow in heart failure. 218 37

There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p less than 0.05), aldosterone (p = 0.003), noradrenaline (p less than 0.001), adrenaline (p = 0.001), and atrial natriuretic factor (p = 0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular.
 ...
PMID:Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. 222 74

In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha-2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta-ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A-mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous "down-regulation" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta-2 ARs are nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. 224 13

To estimate the pumping function of the left-sided heart in patients with "latent" left-sided heart failure due to heart disease which primarily affected the left-side of the heart (former NYHA class I and II), we measured (i) the increase of peripheral venous pressure in response to supine mild leg exercise (delta VP), and (ii) the increase of plasma noradrenaline (NA) concentration due to phentolamine (PH) injection (delta NAPH). We divided the patients into well-functioning left-sided heart group (delta CI/delta PAW greater than 0.180 L.min-1.M-2.mmHg-1) and poorly-functioning left-sided heart group (delta CI/delta PAW less than or equal to 0.180 L.min-1.M-2.mmHg-1) on the basis of a ratio (delta CI/delta PAW), relating the increase in cardiac index (delta CI) in response to exercise to the concomitant increase in mean pulmonary artery wedge pressure (delta PAW). This diving line (delta CI/delta PAW = 0.180 L.min-1.M-2.mmHg-1) correlated with delta VP (diving line: delta VP = 35 mmH2O) and with delta NAPH (diving line: delta NAPH = 0.353 ng/ml). Our results suggest that delta VP and delta NAPH reflected the pumping function of the left-sided heart with considerable accuracy.
 ...
PMID:[Plasma noradrenaline response to phentolamine in "latent" left-sided heart failure]. 232 18

1. Dopexamine is a novel analogue of dopamine which is free of alpha-adrenoceptor activity and is of therapeutic value in chronic heart failure. The effects of dopexamine on the in vitro function of platelets from 10 healthy subjects at rest, after exercise and after in vitro addition of adrenaline and noradrenaline were investigated. 2. Dopexamine in a wide range of concentrations (10(-9)M-10(-3)M) did not appear to function as an agonist on platelets either in whole blood or in PRP preparations. 3. Dopexamine caused a dose-dependent inhibition of agonist-induced platelet aggregation in both whole blood and PRP. The inhibitory effect of dopexamine was significantly greater in PRP than in whole blood, and significantly greater to adrenaline than to collagen or ADP as agonists in whole blood. 4. After exercise or after in vitro addition of adrenaline and noradrenaline at concentrations commonly seen in myocardial infarction, dopexamine produced similar levels of inhibition seen with platelets from resting subjects. 5. Dopexamine did not affect plasma catecholamine levels but caused an increase in intraplatelet noradrenaline levels. 6. This study suggests that dopexamine is unlikely adversely to affect the hyperaggregable state found in patients with cardiogenic shock after myocardial infarction.
 ...
PMID:The effects of dopexamine, a new dopamine analogue, on platelet function in stress. 239 Apr 35

The effects on cardiac function of captopril (CPT) and digoxin (D) were compared in a study of 16 patients with chronic heart failure due to ischemic heart disease (15) and to congestive cardiomyopathy (1) (New York Heart Association class II n.13 and class III n.3). All patients were normotensive and in sinus rhythm. CPT 25 mg every 8 hours (t.i.d.) or D 0.25 mg once daily was given in a single-blind crossover design: A placebo (PLC) t.i.d. was given for 5 to 10 days, then CPT or D, according to a random sequence, replaced three or one of the PLC tablets; after one month, CPT and D were switched to PLC for 5 to 10 days; subsequently, the PLC tablets were replaced by CPT in the patients who previously received D and vice versa, and both treatments were again continued for one month. PLC, CPT, and D tablets were all identical. Diuretics once daily were given throughout the study. Plasma renin activity (PRA), plasma aldosterone (ALDO), plasma noradrenaline (NA), and adrenaline (A) were determined at the end of the two PLC periods and the two active treatments. A hand grip and a bicycle exercise were performed at the end of the two PLC periods and the two active treatments. No difference was noted between the PLC periods. PRA increased with CPT and did not change with D. ALDO was decreased by both CPT and D. NA and A were similarly decreased by both drugs, both supine and standing.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Captopril versus digoxin in mild-moderate chronic heart failure: a crossover study. 244 Dec 3

1 The responses to substance P, isoprenaline and noradrenaline were observed on human isolated coronary arteries removed from 30 human hearts, and were classified according to the age of the hearts, the presence or absence of cardiac failure and the degree of atherosclerosis. 2 The endothelium-dependent vasodilator, substance P (0.1 microM), relaxed rings precontracted with prostaglandin F2 alpha, (PGF2 alpha, 1 microM) when they were devoid of atherosclerosis. The presence of moderate or severe lesions of atherosclerosis abolished this response. There was no difference in the response, related to either the age of the hearts or to the presence or absence of cardiac failure. 3 The dose-response curves to isoprenaline (an endothelium-independent vasodilator) were also markedly altered by the presence of atherosclerotic lesions, while aging and the presence of cardiac failure did not alter the maximal relaxation. These last 2 factors induced only a rightward shift of the dose-response curves. 4 On severely atherosclerotic rings, beta-adrenoceptor-mediated responses were so altered that the effect of noradrenaline was wholly vasoconstrictor (via alpha-adrenoceptors). This response was not modified after pretreatment with atenolol (10 microM). 5 It is concluded that atherosclerosis in human coronary arteries, induces alterations in the responses to substance P and to beta-adrenoceptor agonists. The beta-adrenoceptor-mediated relaxations seem more influenced by the presence of atherosclerosis than they are by aging or by the down-regulation induced by cardiac failure. Conversely, the alpha-adrenoceptor responses appear to be well preserved.
 ...
PMID:The influence of atherosclerosis on the mechanical responses of human isolated coronary arteries to substance P, isoprenaline and noradrenaline. 244 99

The functional significance of alterations in contractile proteins was investigated in the chronically overloaded left ventricle of Goldblatt rats and spontaneously hypertensive rats (SHRs). Congestive cardiac insufficiency occurring in late stages of pressure overload is associated with impaired contractility, as well as significant structural dilatation. Only in the event of extreme dilatation, however, would pumping failure occur in the presence of intact myocardial contractile capability. The transformation toward a slower myocardium is associated with a reduced rate of Ca2+ uptake by the sarcoplasmic reticulum. Transformation influences ventricular and myocardial working capacity to a much lesser extent than do the velocity parameters of contraction. Although a fairly homogeneous VM-3 pattern is typical for ventricles when cardiac failure is experimentally induced, extreme myocardial transformation, as such, does not cause congestive failure. With cardiac insufficiency, left ventricular volume, systolic wall stress, and hydroxyproline concentration are overproportionately increased, as related to VM-3 content, whereas noradrenaline content is decreased. This is consistent with the assumption that myocardial transformation is not necessary for the development of these alterations. Myocardial transformation may be promoted by structural dilatation. Extreme transformation, however, should, in turn, decrease contractility, contributing to cardiac failure. A considerable decrease in contractility indirectly causes depletion of the catecholamine stores. The energy-saving effect of myocardial transformation toward a slower muscle cannot compensate for the unfavorable effects of a substantial degree of ventricular dilatation.
 ...
PMID:Functional significance of contractile proteins in cardiac hypertrophy and failure. 248 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>